The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Abolition of mitochondrial substrate‐level phosphorylation by itaconic acid produced by LPS‐induced Irg1 expression in cells of murine macrophage lineage
Abstract
Itaconate is a nonamino organic acid exhibiting antimicrobial effects. It has been recently identified in cells of macrophage lineage as a product of an enzyme encoded by immunoresponsive gene 1 ( Irg1 ), acting on the citric acid cycle intermediate cis‐aconitate. In mitochondria, itaconate can be converted by succinate‐coenzyme A (CoA) ligase to itaconyl‐CoA at the expense of ATP (or GTP), and is also a weak competitive inhibitor of complex II. Here, we investigated specific bioenergetic effects of increased itaconate production mediated by LPS‐induced stimulation of Irg1 in murine bone marrow‐derived macrophages (BMDM) and RAW‐264.7 cells. In rotenone‐treated macrophage cells, stimulation by LPS led to impairment in substrate‐level phosphorylation (SLP) of in situ mitochondria, deduced by a reversal in the directionality of the adenine nucleotide translocase operation. In RAW‐264.7 cells, the LPS‐induced impairment in SLP was reversed by short‐interfering RNA(siRNA)—but not scrambled siRNA—treatment directed against Irg1. LPS dose‐dependently inhibited oxygen consumption rates (61‐91%) and elevated glycolysis rates (>21%) in BMDM but not RAW‐264.7 cells, studied under various metabolic conditions. In isolated mouse liver mitochondria treated with rotenone, itaconate dose‐dependently (0.5‐2 mM) reversed the operation of adenine nucleotide translocase, implying impairment in SLP, an effect that was partially mimicked by malonate. However, malonate yielded greater ADP‐induced depolarizations (3‐19%) than itaconate. We postulate that itaconate abolishes SLP due to 1) a “CoA trap” in the form of itaconyl‐CoA that negatively affects the upstream supply of succinyl‐CoA from the α‐ketoglutarate dehydrogenase complex; 2) depletion of ATP (or GTP), which are required for the thioesterification by succinate‐CoA ligase; and 3) inhibition of complex II leading to a buildup of succinate which shifts succinate‐CoA ligase equilibrium toward ATP (or GTP) utilization. Our results support the notion that Irg1 ‐expressing cells of macrophage lineage lose the capacity of mitochondrial SLP for producing itaconate during mounting of an immune defense.—Németh, B., Doczi, J., Csete, D., Kacso, G., Ravasz, D., Adams, D., Kiss, G., Nagy, A. M., Horvath, G., Tretter, L., Mócsai, A., Csépányi‐Kömi, R., Iordanov, I., Adam‐Vizi, V., Chinopoulos, C. Abolition of mitochondrial substrate‐level phosphorylation by itaconic acid produced by LPS‐induced Irg1 expression in cells of murine macrophage lineage. FASEB J. 30, 286‐300 (2016). www.fasebj.org
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In 2014 Lee and colleagues demonstrated that acetyl-CoA levels and histone acetylation in tumors are regulated by oncogenic activation of Akt and subsequent ACLY phosphorylation58.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [58]
In the citing paper
“levels of histone acetylation have been shown to be predictive of which patients would later exhibit biochemical failure, with lower levels predictive of worse outcome.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [58]
In the citing paper
“histone acetylation and phosphorylated Akt levels correlate significantly in human glioma and human prostate cancer”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [58]
Citations
Cites
1 retracted
Garedew, A., Henderson, S. O., & Moncada, S. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.27 · Cited by 124
RetractedUnderstanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Succinate is an inflammatory signal that induces IL-1β through HIF-1α
Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., Frezza, C., Bernard, N. J., Kelly, B., Foley, N. H., et al. (2013) · Nature · doi:10.1038/nature11986 · Cited by 4,176
A new collection method for the evaluation of nasal mucus proteins
Ruocco, L. A., Fattori, Romanelli, Martelloni, L., Casani, Samolewska, & Rezzonico (1998) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.1998.00312.x · Cited by 1,296
Toll-like receptor–induced changes in glycolytic metabolism regulate dendritic cell activation
Krawczyk, C. M., Holowka, T., Sun, J., Blagih, J., Amiel, E., DeBerardinis, R. J., Cross, J. R., Jung, E., Thompson, C. B., Jones, R. G., et al. (2010) · Blood · doi:10.1182/blood-2009-10-249540 · Cited by 1,246
Identification of Lps2 as a key transducer of MyD88-independent TIR signalling
Hoebe, K. H. N., Du, X., Georgel, P., Janssen, E. M., Tabeta, K., Kim, S. O., Goode, J., Lin, P., Mann, N., Mudd, S., et al. (2003) · Nature · doi:10.1038/nature01889 · Cited by 1,232
Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production
Michelucci, A., Cordes, T., Ghelfi, J., Pailot, A., Reiling, N., Goldmann, O., Binz, T., Wegner, A., Tallam, A., Rausell, A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218599110 · Cited by 1,191
Rodríguez-Prados, J.-C., Través, P. G., Cuenca, J., Rico, D., Aragonés, J., Martín-Sanz, P., Cascante, M., & Boscá, L. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0901698 · Cited by 1,022
Safranine as a probe of the mitochondrial membrane potential
Åkerman, K. E. O., & Wikström, M. K. F. (1976) · FEBS Letters · doi:10.1016/0014-5793(76)80434-6 · Cited by 793
Succinate: a metabolic signal in inflammation
Mills, E., & O’Neill, L. A. J. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.11.008 · Cited by 741
The ADP and ATP transport in mitochondria and its carrier
Klingenberg, M. (2008) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2008.04.011 · Cited by 643
Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells
Everts, B., Amiel, E., van der Windt, G. J. W., Freitas, T. C., Chott, R., Yarasheski, K. E., Pearce, E. L., & Pearce, E. J. (2012) · Blood · doi:10.1182/blood-2012-03-419747 · Cited by 532
Biotechnological production of itaconic acid
Willke, T., & Vorlop, K. (2001) · Applied Microbiology and Biotechnology · doi:10.1007/s002530100685 · Cited by 513
Biotechnological production of itaconic acid and its biosynthesis in Aspergillus terreus
Okabe, M., Lies, D., Kanamasa, S., & Park, E. Y. (2009) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-009-2132-3 · Cited by 488
Cellular Metabolism and Macrophage Functional Polarization
Zhu, L., Zhao, Q., Yang, T., Ding, W., & Zhao, Y. X. (2014) · International Reviews of Immunology · doi:10.3109/08830185.2014.969421 · Cited by 438
Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses
Kimura, A., Naka, T., Nakahama, T., Chinen, I., Masuda, K., Nohara, K., Fujii‐Kuriyama, Y., & Kishimoto, T. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090560 · Cited by 426
Itaconic acid is a mammalian metabolite induced during macrophage activation
Strelko, C. L., Lu, W., Dufort, F. J., Seyfried, T. N., Chiles, T. C., Rabinowitz, J. D., & Roberts, M. F. (2011) · Journal of the American Chemical Society · doi:10.1021/ja2070889 · Cited by 391
The contributions of respiration and glycolysis to extracellular acid production
Mookerjee, S. A., Goncalves, R. L. S., Gerencser, A. A., Nicholls, D. G., & Brand, M. D. (2014) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2014.10.005 · Cited by 355
LPS induces apoptosis in macrophages mostly through the autocrine production of TNF-α
Xaus, J., Comalada, M., Valledor, A. F., Lloberas, J., López-Soriano, F., Argilés, J. M., Bogdan, C., & Celada, A. (2000) · Blood · doi:10.1182/blood.v95.12.3823 · Cited by 331
Haile, D. J., Rouault, T. A., Harford, J. B., Kennedy, M. C., Blondin, G. A., Beinert, H., & Klausner, R. D. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.24.11735 · Cited by 321
Weinberg, J. M., Venkatachalam, M. A., Roeser, N. F., & Nissim, I. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.6.2826 · Cited by 317
Quantitative Microplate-Based Respirometry with Correction for Oxygen Diffusion
Gerencser, A. A., Neilson, A., Choi, S. W., Edman, U., Yadava, N., Oh, R. J., Ferrick, D. A., Nicholls, D. G., & Brand, M. D. (2009) · Analytical Chemistry · doi:10.1021/ac900881z · Cited by 312
1H NMR-based Metabolomic Profiling in Mice Infected with Mycobacterium tuberculosis
Shin, J.-H., Yang, J.-Y., Jeon, B.-Y., Yoon, Y. J., Cho, S.-N., Kang, Y.-H., Ryu, D. H., & Hwang, G.-S. (2011) · Journal of Proteome Research · doi:10.1021/pr101054m · Cited by 247
Itaconate, an isocitrate lyase-directed inhibitor in Pseudomonas indigofera
McFadden, B. A., & Purohit, S. (1977) · Journal of Bacteriology · doi:10.1128/jb.131.1.136-144.1977 · Cited by 220
Mechanisms underlying the loss of mitochondrial membrane potential in glutamate excitotoxicity
Abramov, A. Y., & Duchen, M. R. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.04.017 · Cited by 213
Bochud‐Allemann, N., & Schneider, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205776200 · Cited by 203
Biochemistry of microbial itaconic acid production
Steiger, M. G., Blumhoff, M. L., Mattanovich, D., & Sauer, M. (2013) · Frontiers in Microbiology · doi:10.3389/fmicb.2013.00023 · Cited by 196
Itaconic Acid: The Surprising Role of an Industrial Compound as a Mammalian Antimicrobial Metabolite
Cordes, T., Michelucci, A., & Hiller, K. (2015) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071714-034243 · Cited by 184
Hypoxia and hypoxia inducible factors in tumor metabolism
Zeng, W., Liu, P., Pan, W., Singh, S. R., & Wei, Y. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.01.032 · Cited by 174
The role of an astrocytic NADPH oxidase in the neurotoxicity of amyloid beta peptides
Abramov, A. Y., & Duchen, M. R. (2005) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2005.1766 · Cited by 158
The proinflammatory cytokine-induced IRG1 protein associates with mitochondria
Degrandi, D., Hoffmann, R., Beuter-Gunia, C., & Pfeffer, K. (2009) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2008.0013 · Cited by 155
[11] The preparation of heart mitochondria from laboratory animals
Tyler, D. D., & Gonze, J. (1967) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(67)10014-1 · Cited by 151
STAT3 regulates NF-κB recruitment to the IL-12p40 promoter in dendritic cells
Hoentjen, F., Sartor, R. B., Ozaki, M., & Jobin, C. (2004) · Blood · doi:10.1182/blood-2004-04-1309 · Cited by 143
Highly Sensitive GC/MS/MS Method for Quantitation of Amino and Nonamino Organic Acids
Kvitvang, H. F. N., Andreassen, T., Adam, T., Villas-Bôas, S. G., & Bruheim, P. (2011) · Analytical Chemistry · doi:10.1021/ac103245b · Cited by 136
Studies on succinate dehydrogenase
Dervartanian, D. V., & Veeger, C. (1964) · Biochimica et Biophysica Acta (BBA) - Specialized Section on Enzymological Subjects · doi:10.1016/0926-6569(64)90182-8 · Cited by 130
Tavakoli, S., Zamora, D. A., Ullevig, S. L., & Asmis, R. (2013) · Journal of Nuclear Medicine · doi:10.2967/jnumed.112.119099 · Cited by 109
A Novel Kinetic Assay of Mitochondrial ATP-ADP Exchange Rate Mediated by the ANT
Chinopoulos, C., Vajda, S., Csanády, L., Mándi, M., Mathe, K., & Ádám‐Vizi, V. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2008.12.3915 · Cited by 104
Self-citationChinopoulos, C., Gerencser, A. A., Mandi, M., Mathe, K., Töröcsik, B., Doczi, J., Turiak, L., Kiss, G., Konràd, C., Vajda, S., et al. (2010) · The FASEB Journal · doi:10.1096/fj.09-149898 · Cited by 103
Self-citationMetabolomic Patterns in Glioblastoma and Changes during Radiotherapy: A Clinical Microdialysis Study
Wibom, C., Surowiec, I., Mörén, L., Bergström, P., Johansson, M., Antti, H., & Bergenheim, A. T. (2010) · Journal of Proteome Research · doi:10.1021/pr901088r · Cited by 101
Non-targeted metabolite profiling in activated macrophage secretion
Sugimoto, M., Sakagami, H., Yokote, Y., Onuma, H., Kaneko, M., Mori, M., Sakaguchi, Y., Soga, T., & Tomita, M. (2012) · Metabolomics · doi:10.1007/s11306-011-0353-9 · Cited by 95
Hypoxia-mediated regulation of macrophage functions in pathophysiology
Riboldi, E., Porta, C., Morlacchi, S., Viola, A., Mantovani, A., & Sica, A. (2012) · International Immunology · doi:10.1093/intimm/dxs110 · Cited by 95
THE METABOLISM OF ITACONIC ACID BY LIVER MITOCHONDRIA
Adler, J., Wang, S., & Lardy, H. A. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)63691-4 · Cited by 88
Coenzyme A and its derivatives: renaissance of a textbook classic
Theodoulou, F. L., Sibon, O. C. M., Jackowski, S., & Gout, I. T. (2014) · Biochemical Society Transactions · doi:10.1042/bst20140176 · Cited by 88
Través, P. G., de Atauri, P., Marín, S., Pimentel-Santillana, M., Rodríguez‐Prados, J., de Mas, I. M., Selivanov, V. A., Martín‐Sanz, P., Boscá, L., & Cascante, M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101781 · Cited by 83
Mitochondrial consumption of cytosolic ATP: Not so fast
Chinopoulos, C. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.04.004 · Cited by 79
Self-citationThe Pathway of Itaconate Metabolism by Liver Mitochondria
Wang, S., Adler, J., & Lardy, H. A. (1961) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64421-7 · Cited by 75
Berg, I. A., Filatova, L. V., & Ivanovsky, R. N. (2002) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2002.tb11413.x · Cited by 71
Naringin inhibits chemokine production in an LPS-induced RAW 264.7 macrophage cell line
Liu, Y., Su, W., WANG, S., & Li, P. (2012) · Molecular Medicine Reports · doi:10.3892/mmr.2012.1072 · Cited by 71
Hillier, S., & Charnetzky, W. T. (1981) · Journal of Bacteriology · doi:10.1128/jb.145.1.452-458.1981 · Cited by 68
Itaconate reduces visceral fat by inhibiting fructose 2,6-bisphosphate synthesis in rat liver
Sakai, A., Kusumoto, A., Kiso, Y., & Furuya, E. (2004) · Nutrition · doi:10.1016/j.nut.2004.08.007 · Cited by 66
Kiss, G., Konrad, C., Doczi, J., Starkov, A., Kawamata, H., Manfredi, G., Zhang, S. F., Gibson, G. E., Beal, M., Ádám-Vizi, V., et al. (2013) · The FASEB Journal · doi:10.1096/fj.12-220202 · Cited by 64
Self-citationSanadi, D. R., Gibson, D. M., & Ayengar, P. (1954) · Biochimica et Biophysica Acta · doi:10.1016/0006-3002(54)90205-x · Cited by 62
The role of succinyl-CoA synthetase in the control of heme biosynthesis.
Labbe, R. E., Kurumada, T., & Onisawa, J. (1965) · Biochimica et Biophysica Acta · doi:10.1016/0304-4165(65)90050-4 · Cited by 61
Lee, Y., Sohn, W., Kim, D., & Kwon, H. (2004) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.2004.04011.x · Cited by 60
Succinic thiokinase and metabolic control.
Ottaway, J., Mcclellan, J. A., & Saunderson, C. (1981) · International Journal of Biochemistry · doi:10.1016/0020-711x(81)90111-7 · Cited by 48
Caenorhabditis elegans and Ascaris suum: inhibition of isocitrate lyase by itaconate
Patel, T. R., & McFadden, B. A. (1978) · Experimental Parasitology · doi:10.1016/0014-4894(78)90107-8 · Cited by 46
Xu, L., Shen, S., Ma, Y., Kim, J. K., Rodríguez‐Agudo, D., Heuman, D. M., Hylemon, P. B., Pandak, W. M., & Ren, S. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00337.2011 · Cited by 45
The inhibitory effects of itaconic acid in vitro and in vivo
Booth, A. N., Taylor, J., Wilson, R. H., & DeEds, F. (1952) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)55778-1 · Cited by 42
The “B Space” of mitochondrial phosphorylation
Chinopoulos, C. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22659 · Cited by 39
Self-citationKiss, G., Konrad, C., Pour-Ghaz, I., Mansour, J. J., Németh, B., Starkov, A., Ádám-Vizi, V., & Chinopoulos, C. (2014) · The FASEB Journal · doi:10.1096/fj.13-243030 · Cited by 39
Self-citationNolte, J., Schürmann, M., Schepers, C.-L., Vogel, E., Wübbeler, J. H., & Steinbüchel, A. (2013) · Applied and Environmental Microbiology · doi:10.1128/aem.03075-13 · Cited by 32
[Methylglutaconase, a new hydrase participating in the metabolism of various carboxylic acids].
Hilz, H., Knappe, J., Ringelmann, E., & Lynen, F. (1958) · PubMed · Cited by 24
Xiao, W., Wang, L., Xiao, R., Wu, M., Tan, J., & He, Y. (2011) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-011-0784-7 · Cited by 13
Hunger‐Glaser, I., Brun, R., Linder, M., & Seebeck, T. (1999) · Molecular and Biochemical Parasitology · doi:10.1016/s0166-6851(99)00032-8 · Cited by 10
Franke, W., Mitarbeit, E. H. U., & Taschen, G. (1957) · Justus Liebig s Annalen der Chemie · doi:10.1002/jlac.19576080115 · Cited by 10
Flagged first, then by citations
Cited by
Sorted by citations
Immunometabolism governs dendritic cell and macrophage function
O'Neill, L. A. J., & Pearce, E. J. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20151570 · Cited by 1,779
Lampropoulou, V., Sergushichev, A., Bambousková, M., Nair, S., Vincent, E. E., Loginicheva, E., Cervantes‐Barragán, L., Ma, X., Huang, S. C., Griss, T., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.06.004 · Cited by 1,583
Macrophage Immunometabolism: Where Are We (Going)?
den Bossche, J. V., O'Neill, L. A. J., & Menon, D. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.03.001 · Cited by 1,187
HIF1α and metabolic reprogramming in inflammation
Corcoran, S. E., & O'Neill, L. A. J. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84431 · Cited by 814
Glycolysis – a key player in the inflammatory response
Soto‐Heredero, G., Heras, M. M. G. D. L., Gabandé‐Rodríguez, E., Oller, J., & Mittelbrunn, M. (2020) · FEBS Journal · doi:10.1111/febs.15327 · Cited by 660
Metadata
- Authors
- Németh, B., Doczi, J., Csete, D., Kacso, G., Ravasz, D., Adams, D., Kiss, G., Nagy, A. M., Horvath, G., Tretter, L., Mócsai, A., Csépáinyi‐Kömi, R., Iordanov, I., Adam‐Vizi, V., & Chinopoulos, C.
- Affiliations
- Department of Medical Biochemistry Semmelweis University Budapest Hungary
- Department of Physiology Semmelweis University Budapest Hungary
- Semmelweis University (HU)
- Corresponding author
- Chinopoulos, Christos
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2015-09-10
- Volume
- 30
- Issue
- 1
- Pages
- 286-300
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2232390838
- Cited by
- 136
- References
- 65
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 9 · 2023: 7 · 2022: 20 · 2021: 14 · 2020: 15 · 2019: 15 · 2018: 11 · 2017: 15 · 2016: 9 · 2015: 1
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- Funders
- Magyar Tudományos Akadémia (02001)
- Hungarian Scientific Research Fund (K 100918)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- itaconic acid, IRG1, substrate-level phosphorylation, macrophages, LPS, complex II inhibition, succinic acid, adenine nucleotide translocase, mitochondrial bioenergetics, glycolysis, rotenone, malonate, alpha-ketoglutarate dehydrogenase complex, succinyl-CoA, ATP depletion, bone marrow-derived macrophages, RAW 264.7 macrophages
- MeSH terms
- Mitochondrial ADP, ATP Translocases, Animals, Cell Line, Chlorocebus aethiops, Female, Glycolysis, Hydro-Lyases, Lipopolysaccharides, Macrophages, Male, Malonates, Mice, Inbred C57BL, Mitochondria, Liver, Oxidative Phosphorylation, Rotenone, Succinates, Succinate-CoA Ligases, COS Cells, Mice, Membrane Potential, Mitochondrial
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
